TY - JOUR T1 - A role of cyclic nucleotides in neuromuscular transmission. JF - Journal of Pharmacology and Experimental Therapeutics JO - J Pharmacol Exp Ther SP - 553 LP - 564 VL - 199 IS - 3 AU - F G Standaert AU - K L Dretchen AU - L R Skirboll AU - V H Morgenroth, 3rd Y1 - 1976/12/01 UR - http://jpet.aspetjournals.org/content/199/3/553.abstract N2 - This research explored the possibility that cyclic nucleotides are part of the excitation-secretion sequence in mammalian motor nerve terminals. A series of reagents known to react with the enzymes that synthesize and degrade cyclic nucleotides or that are effectors of cyclic nucleotide actions were administered to in vivo cat soleus nerve-muscle preparations. The reagents were administered by rapid close intra-arterial injection while electrical activity in single motor axons and contractile activity of the muscle were monitored. NaF, an activator of adenylate cyclase, evoked bursts of action potentials in unstimulated axons and caused stimulus-bound repetitive activity in stimulated axons. It evoked vigorous asynchronous activity in the muscle and potentiated the force of muscle contraction. These effects are identical with those of cyclic N6-2'-O-dibutyryl adenosine 3':5'-monophosphate (dibutyryl cAMP). Prostaglandin E1 produced similar effects. Dithiobisnitrobenzoic acid and alloxan, inhibitors of adenylate cyclase, impaired neuromuscular transmission and prevented the effects of NaF, but they did not change the responses to dibutyryl cAMP. Theophylline, an inhibitor of phosphodiesterase, caused axons to respond repetitively to stimulation, but this activity had a different pattern from that produced by dibutyryl cAMP or NaF. Pretreatment with theophylline enhanced the responses to dibutyryl cAMP and NaF. Imidazole, an activator of phosphodiesterase, impaired neuromuscular transmission and prevented the effects of dibutyryl cAMP and NaF. Adenosine, an inhibitor of protein kinase, or verapamil, which inhibits calcium flux, impaired neuromuscular transmission and prevented the responses to dibutyryl cAMP, NaF and theophylline. These results are compatible with the hypothesis that cAMP is involved in the regulation of calcium flux and transmitter secretion in mammalian motor nerve terminals. ER -